非小細胞肺癌放射治療進展課件

1影像技術(shù)和計算機技術(shù)的進步為精確放射治療的實現(xiàn)

提供可能1影像技術(shù)和計算機技術(shù)的進步為精確放射治療的實現(xiàn)

提供可能22334屏氣技術(shù)舉例:ElektaABC4屏氣技術(shù)舉例:ElektaABC5四維CT影像技術(shù)呼氣吸氣螺旋開始時相由吸轉(zhuǎn)呼呼氣末由呼轉(zhuǎn)吸由吸轉(zhuǎn)呼呼氣吸氣螺旋開始呼吸曲線床位5四維CT影像技術(shù)呼氣吸氣螺旋開始時相由吸轉(zhuǎn)呼呼氣末由呼轉(zhuǎn)吸6影像引導放射治療技術(shù)

IGRT

40對葉片MLCKV級X射線球管KV級探測器陣列MV級探測器陣列6影像引導放射治療技術(shù)

IGRT40對葉片MLCKV級X射7在線校正—影像匹配7在線校正—影像匹配involvedlymphnodesOperableⅢa-N2Grade2:4.Grage4:1.paclitaxel200mg/m2757(P=0.Totalcases 38/281(13.RTisbetterthanOBS.RTisbetterthanOBS.ConcurrentChemo/RadioFavorGrHRbenefit%sur%

2y5y2y5ySEQCON-QDCON-BID二、早期非小細胞肺癌的放射治療UpdateofPORTLungCancer,2005.Pulmonarydisease: Positive:172,Negative:109G3急性和晚期非血液系統(tǒng)毒性：PV:順鉑/長春花堿SEQCON-QDCON-BIDPORT既能夠提高OS也能夠提高DSSNosurvivalbenefitoverconcurrenttherapyalone8一、放射治療在肺癌治療中的地位二、早期NSCL的放射治療三、局部晚期NSCL的放療/化療綜合治療四、3DCRT提高NSCLC的生存率五、術(shù)后放射治療involvedlymphnodes8一、放射治療在肺癌9一、放射治療在肺癌治療中的地位應用循證醫(yī)學的方法評價放射治療在肺癌治療中的地位。9一、放射治療在肺癌治療中的地位應用循證醫(yī)學的方法評價放射治every3weeksX2cyclesFavorGrHRbenefit%sur%

2y5y2y5y5%為復發(fā)和進展病例的治療（laterforrecurrenceorprogression）局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放療OperableⅢa-N2ASCO2007:Abstract7512.Epub2007Apr9%15.PORT既能夠提高OS也能夠提高DSSArimoto 60Gy/8fr/11d92%(22/24)24MpN2降低局部復發(fā)

對OS無明確結(jié)論147patients1、CombinedTreatment：G3急性和晚期非血液系統(tǒng)毒性：結(jié)論：序貫放療/化療優(yōu)于單純放射治療5年生存率8.RTisbetterthanOBS.RT在SCLC治療中的地位10every3weeksX2cycles1011RT在SCLC治療中的地位53.6%±3.3%SCLC病例在其疾病的不同時期需要接受放射治療

45.4%±4.3%

為首程治療（intheinitialtreatment）.

8.2%±1.5%

為復發(fā)和進展病例的治療（laterforrecurrenceorprogression）11RT在SCLC治療中的地位53.6%±3.3%SC12RT在NSCLC治療中的地位64.3%±4.7%ofNSCLCcasesrequireRT.

45.9%±4.3%intheirinitialtreatment.

18.3%±1.8%laterinthecouseoftheillness12RT在NSCLC治療中的地位64.3%±4.7%13二、早期非小細胞肺癌的放射治療

放射治療能夠使早期NSCLC獲得治愈

13二、早期非小細胞肺癌的放射治療放射治療能夠使14JapaneseStudies

I期NSCLC大劑量分割SRT獲得滿意的局部控制率

Institute Dose/fx/OTT

LC/Follow-up Uematsu 50-60/5-10/5d94%

(47/50)36M Kyoto 48Gy/4fr/12d96%

(49/51)20M

Arimoto 60Gy/8fr/11d92%

(22/24)24M Onimaru

60Gy/8fr/11d:88%

(50/57)18MNagataY,KyotoUniv,IASLC,200414JapaneseStudies

I期NSCLC大劑量分15SummaryofJapaneseStudies

Totalcases： 281Age: 39-92(median76)yearsPulmonarydisease: Positive:172,Negative:109Histology: Sqamous:122 Adeno:131, Others:28Stage: IA:178, IB:103Tumordiameter: 7-58(median23)mmMedicalOperability:

Inoperable:177, Operable:

104OnishiH,ASCO200415SummaryofJapaneseStudies

16LocalControlandComplicationFollow-upperiod 2-128(median30)monthsLocalresponse CR26.9% PR59.1% NC14.0%Pneumonitis(NCI-CTC) Grade0:33.7% Grade1:59.9% Grade2:4.0% Grade3:1.2% Grage4:1.2%Esophagitis(Grade3) 1.2%Pleuraleffusion(transient) 1.6%Ribfracture 1.2%Bonemarrowsuppression 0.0%OnishiH,ASCO200416LocalControlandComplicati17LocalFailureRatesTotalcases 38/281(13.5%) BED<100Gy 21/70(30.0%) BED>100Gy 17/211(8.1%)StageIA 17/177(9.6%)

BED<100Gy 8/41(19.5%) BED>100Gy 9/136(6.6%)StageIB 21/102(20.6%) BED<100Gy 13/29(44.8%) BED>100Gy 8/73(11.0%)Adenocarcinoma 17/122(14.0%)Squamouscellca. 18/131(13.7%)OnishiH,ASCO200417LocalFailureRatesTotalcas18Mountain*JCOG*JNCCH*StageIAStageIB67%57%80%63%74%53%STI**90%

84%*Surgery**StereotacticIrradiationComparisonof5-YrOverallSurvivalBetweenSurgery&STISurvivalcurvesofoperableptsirradiated

withBEDof100GyormoreaccordingtoStagestageIA(n=47)stageIB(n=16)p=0.2OverallSurvivalTime(years)SummaryofJapaneseStudiesOnishiH,ASCO200418Mountain*JCOG*JNCCH*StageI19I期非小細胞肺癌立體定向放射治療或楔形切除后的轉(zhuǎn)歸SRBT(n=55)楔形切除(n=69)P肺功能（FEV-1）1.39(0.86-2.37)1.31(0.52-3.0)NSCharlson合并癥指數(shù)

3(1-4)4(3-6)<0.01年齡74(69-78)78(55-89)<0.01分期T1-T2T1-T2NS病變最大直徑GTV:2.3(1-5.3)手術(shù)標本：1.7(0.4-4.7)-縱隔淋巴結(jié)轉(zhuǎn)移0(PET,縱隔鏡)0(手術(shù))NS化療16%10%NSGrillsetal:19I期非小細胞肺癌立體定向放射治療或楔形切除后的轉(zhuǎn)歸SRB20I期非小細胞肺癌立體定向放射治療或楔形切除后的轉(zhuǎn)歸20I期非小細胞肺癌立體定向放射治療或楔形切除后的轉(zhuǎn)歸21作者患者MFUTRRorLRDMOSCSSGinsberg,19951225417-6175Landreneau,1997422924-5838*602416-6538*Sienel,2007495416--67Sienel,200856451618-713145556-48Keenan,200454271196274El-Sherif,20062073171540-Lee,200335516304761Voynov,2005110414818-Birdas,200641255-54-27250---142514---I期非小細胞肺癌局部切除后的轉(zhuǎn)歸21作者患者MFUTRRorLRDMOSCSSGinsb60mg/m2weekly2GyBID)day1DocetaxelFavorGrHRbenefit%sur%

2y5y2y5yHannaetal.DDP40-120mg/m2/cycle,totaldose120-800mg/m2

radiationdose50Gy/20f-65Gy/30f108–116,2006Albainetal.Institute Dose/fx/OTTLC/Follow-upI期非小細胞肺癌立體定向放射治療或楔形切除后的轉(zhuǎn)歸PneumonitisRT1%33.FEV-1>1literatstudyentry地位的確立，是肺癌治療進展中CT+SurgeryvsCT/RTRadiationOncologyBiol.DDP40-120mg/m2/cycle,totaldose120-800mg/m2

radiationdose50Gy/20f-65Gy/30f3Dvs2DinMEDICALLYINOPERABLEpN3病例及N分期不明者ThreeClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLC22作者患者MFUTRRorLRDMOSCSSOnisi,2007257388-14206590Negata,20054536216-3183-Uematsu,200150306146688Zimmerman,2006681712165173Fakiris,2009705012134382RTOG,0236552561572-I期非小細胞肺癌立體定向放射治療后的轉(zhuǎn)歸60mg/m2weekly22作者患者MFUTRRor2323242425早期非小細胞肺癌的放射治療

放射治療成為早期NSCLC的另一根治性治療手段放射治療在早期NSCLC治療中的地位的確立，是肺癌治療進展中的一個里程碑25早期非小細胞肺癌的放射治療放射治療成為早期NSCLC的三、局部晚期NSCLC的治療三、局部晚期NSCLC的治療局部晚期NSCLC

EvolutionofTreatmentStrategy

Operable：

Surgery

Surgery±RTSurgery±RT±CT

CT+Surgery

RT/CT+SurgeryRT/CT±Surgery

RT/CT局部晚期NSCLCEvolutionofTreat局部晚期NSCLC

EvolutionofTreatmentStrategy

Inoperable:

RT

CT+RTSequential

CT/RTConcurrent?InductionCTCT/RTCT/RTConsolidation?

局部晚期NSCLCEvolutionofTreneutropeniaandoverallmaximaltoxicityPercentofpatientssurvivingT3-4diseaseRRosell,MDeLena,FCarpagnano,RRamlau,JLGonzalez-Larriba,TGrodzki,ALeGroumelec,DAubert,JGasmi,JYDouillardInductionChemotherapyFollowedbyChemoradiotherapyWithChemoradio-therapyAloneforRegionallyAdvanced

UnresectableStageIIINon–Small-Cell

Lung:CancerandLeukemiaGroupB

CALGB39801中位生存期（月）13.從隨機分組開始后的月數(shù)BED<100Gy 21/70(30.EORTC08941同步:PV/RT(60Gy,2GyQD)day1Cisplatin50mg/m2IVd1,8,29,36

Etoposide50mg/m2IVd1-5&29-33

ConcurrentRT59.同時化放療vs序貫化放療(2)綜合治療5年生存率8.22trails3033cases34月22月＜70vs≥70歲Grade1:59.Pulmonarydisease: Positive:172,Negative:109Inoperable序貫放化綜合治療同步放化綜合治療OperableⅢa-N2RT/CT+SurgeryvsRT/CTCT+SurgeryvsCT/RTneutropeniaandoverallmaxima早期NSCLC獲得治愈Squamouscellca.有無術(shù)后放療組的非腫瘤死亡率并無差異（p=0.CT+RTSequential手術(shù)后3個月內(nèi)腫瘤進展者材料與方法——排除標準ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.2003;(abstract2499)Albainetal.Sienel,2007pN0pN1有害楔形切除(n=69)Bonemarrowsuppression 0.NC14.SEQCON-QDCON-BID757(P=0.1999;17:2692-2699Pulmonarydisease: Positive:172,Negative:109PORT既能夠提高OS也能夠提高DSS203patients序貫化放療薈萃（META）分析22trails3033cases

FavorGrHRbenefit%sur%

2y5y2y5yChemo0.9032R+DDP0.8742151957

p=0.005

DDP40-120mg/m2/cycle,totaldose120-800mg/m2

radiationdose50Gy/20f-65Gy/30f結(jié)論：序貫放療/化療優(yōu)于單純放射治療早期NSCLC獲得治愈序貫化放療薈萃（META）分析結(jié)論：序同時化放療vs序貫化放療同時化放療vs序貫化放療

同時化放療vs序貫化放療(1)

序貫化放療同時化放療5年生存率8.9%15.8%P=0.04。中位生存期（月）13.316.53yLRFSur.21.1%33.9%同時化放療:提高局部控制率和生存率FuruseK,etal.JClin.Oncol.1999;17:2692-2699非小細胞肺癌放射治療進展課件RTOG9410:III期NSCLC

同步放化療vs序貫放化療

序貫:PV-->RT(60Gy,2GyQD)day50

同步:PV/RT(60Gy,2GyQD)day1

同步/HFRT:PE/HFRT(69.2Gy,1.2GyBID)day1 PV:順鉑/長春花堿

PE:順鉑/oral足葉乙甙

RT:放療;QD:每日一次;HFRT:超分隔放療Curran:ASCO,2000;updatedIASLC2000;ASTRO2001,2003RANDOMIZERTOG9410:III期NSCLC

同步放化療vs二.同時化放療vs序貫化放療(2)SEQCON-QDCON-BID

中位生存期：14.61715.6（月）

4年生存率：12%21%17%p=0.046

G3急性和晚期非血液系統(tǒng)毒性：

30%，48%，62%和14%，15%，16%。CurranWetal.Pro.AmSocClinOncol.J.Clin.Oncol.2003;(abstract2499)

二.同時化放療vs序貫化放療(2)**StereotacticIrradiationRT/CT+SurgeryvsRT/CTDDP+Vp16/RT3DCRT能夠提高NSCLC

的治療療效Negata,2005材料與方法——排除標準RadiationPneumonitisandRT在SCLC治療中的地位G3急性和晚期非血液系統(tǒng)毒性：&Table4.9%15.30%，48%，62%和14%，15%，16%。TheMSTwithEP/XRTwashigherthanhistoricalcontrols;3DCRTvs常規(guī)放療

中國醫(yī)學科學院腫瘤醫(yī)院

2001-2006隨訪資料RTOG9410:III期NSCLC

同步放化療vs序貫放化療El-Sherif,2006Pulmonarydisease: Positive:172,Negative:1095年生存率8.**StereotacticIrradiation非小細胞肺癌放射治療進展課件結(jié)論：

同步放化療優(yōu)于序貫放化療，但是，急性毒性反應增加結(jié)論：

同步放化療優(yōu)于序貫放化療，但是，急性毒性反應增加同步放化療？誘導化療?鞏固化療同步放化療？誘導化療?鞏固化療同步放化療誘導化療同步放化療誘導化療InductionChemotherapyFollowedbyChemoradiotherapyWithChemoradio-therapyAloneforRegionallyAdvanced

UnresectableStageIIINon–Small-Cell

Lung:CancerandLeukemiaGroupB

CALGB39801JClinOncol.2007May1;25(13):1698-704.Epub2007AprInductionChemotherapyFolloweCALGB39801studydesignJuly1998andwasclosedinMay2002,Totally366patientsregisteredCALGB39801studydesignJuly1Survival

intent

to

treatSurvivalintenttotreatSurvivalofeligiblepatientswitha

weightlossof≤5%SurvivalofeligiblepatientsDiscussion

增加毒性

inductionchemotherapyincreasesneutropeniaandoverallmaximaltoxicity

沒有生存優(yōu)勢

Nosurvivalbenefitoverconcurrenttherapyalone同期放化療是標準的治療模式

Concomitantchemoradiotherapyiscurrentstandard

therapyforunresectablestageIIIBNSCLCDiscussion增加毒性inductionche60mg/m2weeklySienel,2007FEV-1>1literatstudyentryCT+SurgeryASCO2005.1%33.2、NewRadiationTechniques:Squamouscellca.MonthsSinceRegistrationConcurrentChemo/Radio序貫:PV-->RT(60Gy,2GyQD)day50R+DDP0.3DCRTvs常規(guī)放療

中國醫(yī)學科學院腫瘤醫(yī)院

2001-2006RT在SCLC治療中的地位108–116,2006隨訪資料放射治療成為早期NSCLC的另一同步:PV/RT(60Gy,2GyQD)day1NEvents 中位生存PV:順鉑/長春花堿SimultaneousChemoradiotherapyComparedWithRadiotherapyAloneAfterInductionChemotherapyinInoperableStageIIIAorIIIBNon–Small-CellLungCancer:StudyCTRT99/97bytheBronchialCarcinomaTherapyGroupRudolfM.Huber,MichaelFlentje,MichaelSchmidt,BarbaraP?llinger,HelgaGosse,JochenWillner,andKurtUlmPCx3誘導化療RandomizeRTaloneRT+Paclitaxel60mg/m2weekly60mg/m2weeklySimultaneousChepaclitaxel200mg/m2carboplatinAUC=6every3weeksX2cyclespaclitaxel60mg/m2weeklyRadiotherapyalonepaclitaxel200mg/m2paclitaxe非小細胞肺癌放射治療進展課件SurvivalafterinductionchemotherapyforpatientswithcompleteorpartialresponseSurvivalafterinductionchemo同步放化療鞏固化療同步放化療鞏固化療SWOG9504:同步放化療后應用泰索帝

鞏固化療治療IIIb期NSCLC順鉑/VP-16 X XRT泰索帝 XXX

順鉑50mg/m2d1,8,29,36VP-1650mg/m2d1-5,29-33RT:61Gy:45Gy(1.8Gy/fx),16Gy縮野(2Gy/fx)泰索帝:75mg/m2cycle1-->100mg/m2cycle2-3

SWOG9504:同步放化療后應用泰索帝

SWOG9504:總生存%%%%%020406080100%012243648入組時間（月）

NEvents 中位生存83 45 26月2年生存率:54%3年生存率:37%SWOG9504:總生存%%%%%02040608010

SWOG9504和SWOG9019比較研究病例MST(月)2年生存3年生存S9019(PE/RTPE)5015(10-22)*

34%(21-47)*17%(7-27)*S9504(PE/RT泰索帝)8326(18-35)*54%(43-65)*37%(22-52)**95%CISWOG9504和SWOG9019比較研究病例MSSWAG0023ConcurrentChemo/RadioDDP+Vp16/RTConsolidationChemoDocetaxelMaintenanceGEFITINIBorPLACEBOSWAG0023ConcurrentChemo/Radi非小細胞肺癌放射治療進展課件同步放化療鞏固化療ResultsofASCO2007同步放化療鞏固化療ResultsofASCO2007Logrankp=0.involvedlymphnodesR+DDP0.IIIavsIIIb108–116,200660mg/m2weeklyGrade3:1.Pleuraleffusion(transient) 1.（intheinitialtreatment）.Localresponse CR26.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.Abstract7014.Pneumonitis序貫化放療同時化放療2年OS下降7％55%----48%Surgery±RT±CTROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.pN3病例及N分期不明者HOGLUN01-24PhaseIIIStudyDesignHannaetal.ASCO2007:Abstract7512.ChemoRTCisplatin50mg/m2IVd1,8,29,36

Etoposide50mg/m2IVd1-5&29-33

ConcurrentRT59.4Gy(1.8Gy/fr)Stratification

atrandomization

PS0-1vs2IIIAvsIIIBCRvsnon-CR

InclusionatbaselineUnresectablestageIIIAorIIIB

NSCLCECOGPS0-1atstudyentry

(+PS2atrandom)FEV-1>1literatstudyentry203patients147patients73patients74patientsTaxotere

75mg/m2q3wk3ObservationPrimaryendpoint:OSSecondaryendpoints:PFS,toxicityLogrankp=0.HOGLUN01-24PhasHOGLUN01-24:OS(ITT)

RandomizedPatients(n=147)Hannaetal.ASCO2007:Abstract7512.MonthsSinceRegistration0102030405060Percentofpatientssurviving0%25%50%75%100%P-value:0.940Median3year

survivalrateObservation18.0-34.227.6%Taxotere17-34.827.2%HOGLUN01-24:OS(ITT)

RandomComparisonofGrade3-5ToxicitiesToxicitySWOG9504SWOG0023HOG01-24FebrileNeutropenia

PE/XRT

Docetaxel

NR9%~5%*~5%*9.9%10.9%Esophagitis17%~14%17.2%Pneumonitis7%7%8.2%Docetaxel-relateddeath4.8%4%5.5%*reportedas“infectionwithneutropenia”

ComparisonofGrade3-5ToxiciHogLUGNo1-20/USO-023

TheMSTwithEP/XRTwashigherthanhistoricalcontrols;

ConsolidationDdoesnotfurtherimprovesurvival,isassociatedwithsignificanttoxicityincludinganincreasedrateofhospitalizationandprematuredeath,AndshouldnolongerbeusedforptswithunresectablestageIIINSCLCConclusionsHogLUGNo1-20/USO-023TheM60術(shù)前同時化放療的臨床研究60術(shù)前同時化放療的臨床研究61可手術(shù)（Operable）ⅢA(N2)

放/化療vs放化療+手術(shù)

RTOG93-09INT：0139

61可手術(shù)（Operable）ⅢA(N2)

放62CT/RT/S

145/202CT/RT

155/194Logrankp=0.24危險比=0.87(0.70,1.10)存活率%0255075100從隨機分組開始后的月數(shù)01224364860死亡/總數(shù)INT0139試驗:總生存中位FU81個月Albainetal.

ASCO2005.Abstract7014.62CT/RT/S145/202LogrankpObservationROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.BED<100Gy 13/29(44.SWOG9504:總生存Grade3:1.Cisplatin50mg/m2IVd1,8,29,36

Etoposide50mg/m2IVd1-5&29-33

ConcurrentRT59.108–116,2006同步/HFRT:PE/HFRT(69.Docetaxel地位的確立，是肺癌治療進展中108–116,2006Surgery±RTSurgery±RTFuruseK,etal.ThreeClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLCpN2降低局部復發(fā)

對OS無明確結(jié)論7%ofNSCLCcasesrequireRT.108–116,2006放射治療成為早期NSCLC的另一HOGLUN01-24:OS(ITT)

RandomizedPatients(n=147)3%intheirinitialtreatment.63隨機分組后的月數(shù)

MS3yrOS5yrOS19月

36%22%CT/RT/SCT/RT存活率%025507510001224364860//////////29月

45%24%死亡/總計CT/RT/S38/51CT/RT42/51Logrankp=NSINT0139試驗:肺切除亞組和相應化療/放療亞組的總生存的比較Albainetal.

ASCO2005.Abstract7014.Observation63隨機分組后的月數(shù)MS19月C64Logrank

p=0.002CT/RT/S

57/90CT/RT

74/90死亡/總計存活率%0255075100隨機分組后的月數(shù)01224364860///////////////////////MS34月22月5yrOS36%18%CT/RT/SCT/RTINT0139試驗:

肺葉切除亞組和相應化療/放療亞組的總生存的比較Albainetal.

ASCO2005.Abstract7014.64Logrankp=0.002CT/RT/S5656566

EORTC08941ⅢA：UnresectablepN2不能手術(shù)的ⅢApN2病例通過誘導化療后成為可手術(shù)病例是選擇手術(shù)還是選擇放療？66EORTC08941不676768686969707071四、NSCLC術(shù)后放射治療NewdatasupportsPORTinN2cases71四、NSCLC術(shù)后放射治療Newdatasuppor721998PORT死亡風險增加21%2年OS下降7％55%----48%pN0pN1有害pN2降低局部復發(fā)

對OS無明確結(jié)論PORTMeta-analysisLancet,1998.352:257-63UpdateofPORTLungCancer,2005.47:81-3721998PORT死亡風險增加21%PORTMeta73NewData1

回顧分析PORTSEER1988年～2001年Ⅱ、Ⅲ期NSCLC7465例根治性術(shù)后PORT3508例（47%）SEERJClinOncol,2006.24:2998-3006

預后－多因素分析HR95%CIPolderage1.0251.022-1.0280.0001T3-4disease1.2881.117-1.4840.0005N2nodaldisease1.2811.101-1.4900.0014greaternumberofinvolvedlymphnodes1.0431.027-1.0600.0001PORT1.0480.987-1.1130.126973NewData1

回顧分析PORTSEER198874PORT在N2中的作用N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能夠提高OS也能夠提高DSSN0N1N274PORT在N2中的作用N0N1N2SSRSSRSSR5y75NewData2ResultsfromANITA:PhaseIIIAdjuvantVinorelbineandCisplatinversusObservationinCompletelyResectedNon-Small-CellLungCancerPatientsRRosell,MDeLena,FCarpagnano,RRamlau,JLGonzalez-Larriba,TGrodzki,ALeGroumelec,DAubert,JGasmi,JYDouillard

onbehalfoftheAdjuvantNavelbineInternationalTrialAssociation75NewData2RRosell,MDeLen76CTRTCTRTOBSPORTinN1PatientsRTisbetterthanOBS.ForpatientwhocannottolerateCT,RTwouldberecommended.76CTRTCTRTOBSPORTinN1PatieCTRTCTRTOBSPORTinN2Patients0.000.250.500.751.00DURATIONOFSURVIVAL(MONTHS)020406080100120CT&RTisthebestRTisbetterthanOBSCTRTCTRTOBSPORTinN2Patient78NewData3from

CancerHospital&InstituteofCAMS根治性切除NSCLCT1-3,N2具備完整治療信息一般臨床資料術(shù)中所見及術(shù)后病理治療模式及參數(shù)隨訪資料78NewData3from

CancerHosp79材料與方法——排除標準T4N2者pN3病例及N分期不明者手術(shù)后3個月內(nèi)死亡的患者手術(shù)后3個月內(nèi)腫瘤進展者單純探查術(shù)或縱隔鏡活檢術(shù)79材料與方法——排除標準T4N2者80材料與方法全組例數(shù)PORT無PORT術(shù)式肺葉切除19784113全肺切除241212清掃淋巴結(jié)數(shù)目總數(shù)（枚）1-603-601-60中位數(shù)（枚）21192280材料與方法全組例數(shù)PORT無PORT術(shù)式肺葉切除1978OS例數(shù)MST(月)1年3年5年χ2P值無PORT12531.977.645.430.65.2350.046PORT9643.994.859.134.3生存率OS例數(shù)MST(月)1年3年5年χ2P值無PORT1253DFS1年3年5年χ2P值無PORT56.4910.009PORT76.139.832.1DFSDFS1年3年5年χ2P值無PORT56.428.216治療模式與生存率項目例數(shù)MST(月)1年OS3年OS5年OSS+C+R6148.396.7%63.9%38.2%S+R3538.391.4%51.0%33.7%S+C10033.182.0%46.7%31.9%S2521.661.5%38.5%23.1%治療模式與生存率項目例數(shù)MST(月)1年OS3年OS5年O非腫瘤死亡項目

例數(shù)無術(shù)后放療術(shù)后放療組

心功能衰竭10心肌梗死10小腦萎縮10急性胰腺炎10膿胸10腦血管意外11肺部感染21氣管食管瘺01肺栓塞01不明原因消瘦01死亡原因不明22合計107有無術(shù)后放療組的非腫瘤死亡率并無差異（p=0.493）

非腫瘤死亡項目例數(shù)無術(shù)后放療術(shù)后放療組S+C+RS+CS+RS5yOS47.0%34.0%21.3%16.6%5yOS38.2%31.9%

33.7%23.1%MST（M）47.423.822.712.7MST（M）48.333.138.321.6ANITA的結(jié)果醫(yī)科院腫瘤醫(yī)院的結(jié)果完全切除的ⅢAN2NCSLC推薦術(shù)后化療+放療S+C+R5yOS5yOSMST（M）MST（M）ANITA86AbsoluteVolumeoflungreceived30GyRP(%)NORP(%)P≥340cm329.2(7/24)70.8(17/24)0.003<340cm32.5(1/40)97.5(39/40)PORTcanbesafelyusedwith3DCRTGraph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).Graph1.&Table4.ROCcurse:TheareaundercurveinreceiveroperatingcharacteristiccurvesbasedontherelationshipbetweenincidenceofRPandthevalueofVipsi-dosewas0.757(P=0.020).JiWeietal:ASTROmeeting2008BostonConclusion：ItwassafeforpatientswithNSCLCtoreceivepostoperative3DCRT，ifirradiationdosetolungtissuewaswelldefined.86AbsoluteVolumeoflungrece873DCRT能夠提高NSCLC

的治療療效873DCRT能夠提高NSCLC

的治療療效88Int.J.RadiationOncologyBiol.Phys.,Vol.66,No.1,pp.108–116,20063Dvs2DinMEDICALLYINOPERABLESTAGEINON–SMALL-CELLLUNGCANCER(a)Overallsurvival(b)Disease-specificsurvival88Int.J.RadiationOncologyB89Int.J.RadiationOncologyBiol.Phys.,Vol.66,No.1,pp.108–116,20063Dvs2DinMEDICALLYINOPERABLESTAGEINON–SMALL-CELLLUNGCANCERLocal-regionalcontrol89Int.J.RadiationOncologyB903DCRTvs常規(guī)放療

中國醫(yī)學科學院腫瘤醫(yī)院

2001-2006

903DCRTvs常規(guī)放療

中國醫(yī)學科學院腫瘤91ⅠⅡ期NSCLC

適形放療vs常規(guī)放療91ⅠⅡ期NSCLC

適形放療vs常規(guī)放療92局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放療分組例數(shù)1年3年5年MST常規(guī)放療27561.013.88.015.63-DCRT21873.326.114.420.15年OS6.4%MST4.5月92局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放93局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放療分組例數(shù)1年3年5年常規(guī)放療27565.116.711.23-DCRT21879.033.320.893局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放94OS單因素及多因素COX分析變量單因素多因素危險比P值危險比P

值＜70vs≥70歲1.0350.744------------女性vs男性1.0750.552------------體重下降(＜5%vs≥5%)1.1220.370------------吸煙(無vs有)1.0740.522------------KPS(≥80vs＜80)1.6710.0001.5630.001IIIavsIIIb1.2640.0311.2160.089非鱗癌vs鱗癌1.0510.619------------Hb(≥120vs＜120g/L)1.6250.0001.4220.008化學治療(無vs有)0.8660.138------------50-60vs60vs＞60Gy0.7850.0010.8520.046常規(guī)放療vs三維適形0.7370.0020.7620.009CR+PRvsSD+PD1.6070.0001.5710.00194OS單因素及多因素COX分析變量單因素多因素危險比P值95局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放療2D3DX2P值例數(shù)（比例%）例數(shù)（比例%）食管炎＜2級135（61.9）180（65.5）0.6560.450≥2疾83（38.1）95（34.5）放射性肺炎＜2級148（67.9）202（73.5)1.8290.194≥2疾70（32.1）73(26.5)食管炎＜3級207（95.0）264（96.0）0.3120.662≥3疾11（5.0）11（4.0）放射性肺炎＜3級192(88.5)251(91.3)1.0550.363≥3疾25(11.5)24(8.7)95局部晚期NSCLC（ⅢA/B）

3DCRTvs常規(guī)放96結(jié)論與常規(guī)放射治療技術(shù)相比3DCRT能夠提高NSCLC的生存率推薦3DCRT作為非小細胞肺癌的標準治療技術(shù)96結(jié)論與常規(guī)放射治療技術(shù)相比3DCRT能夠提高NSCLC97ThreeClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLC1、CombinedTreatment：

ConcurrentChemoradiotherapy同時放化療中化療方案的選擇誘導化療或鞏固化療的必要性和化療方案放射治療與生物靶向治療的聯(lián)合應用97ThreeClinicalResearchTopi98ThreeClinicalResearchTopicsinRadiotherapyofLocallyAdvancedNSCLC2、NewRadiationTechniques:3DRT，IMRT,IGRT,4DRT3、NormalTissueProtection：

RadiationPneumonitisandEsophagitis

98ThreeClinicalResearchTopi99謝謝99謝謝100LocalControlandComplicationFollow-upperiod 2-128(median30)monthsLocalresponse CR26.9% PR59.1% NC14.0%Pneumonitis(NCI-CTC) Grade0:33.7% Grade1:59.9% Grade2:4.0% Grade3:1.2% Grage4:1.2%Esophagitis(Grade3) 1.2%Pleuraleffusion(transient) 1.6%Ribfracture 1.2%Bonemarrowsuppression 0.0%OnishiH,ASCO2004100LocalControlandComplicat同時化放療vs序貫化放療同時化放療vs序貫化放療RTOG9410:III期NSCLC

同步放化療vs序貫放化療

序貫:PV-->RT(60Gy,2GyQD)day50

同步:PV/RT(60Gy,2GyQD)day1

同步/HFRT:PE/HFRT(69.2Gy,1.2GyBID)day1 PV:順鉑/長春花堿

PE:順鉑/oral足葉乙甙

RT:放療;QD:每日一次;HFRT:超分隔放療Curran:ASCO,2000;updatedIASLC2000;ASTRO2001,2003RANDOMIZERTOG9410:III期NSCLC

同步放化療vs二.同時化放療vs序貫化放療(2)SEQCON-QDCON-BID

中位生存期：14.61715.6（月）

4年生存率：12%21%17%p=0.046

G3急性和晚期非血液系統(tǒng)毒性：

30%，48%，62%和14%，15%，16%。CurranWetal.Pro.AmSocClinOncol.J.Clin.Oncol.2003;(abstract2499)

二.同時化放療vs序貫化放療(2)非小細胞肺癌放射治療進展課件105105106PORT在N2中的作用N0N1N2SSRSSRSSR5yOS41%31%34%30%20%27%DSS53%39%44%38%27%36%P0.04350.01960.0077PORT既能夠提高OS也能夠提高DSSN0N1N2106PORT在N2中的作用N0N1N2SSRSSRSSR5107Int.J.RadiationOncologyBiol.Phys.,Vol.66,No.1,pp.108–116,20063Dvs2DinMEDICALLYINOPERABLESTAGEINON–SMALL-CELLLUNGCANCERLocal-regionalcontrol107Int.J.RadiationOncology108影像技術(shù)和計算機技術(shù)的進步為精確放射治療的實現(xiàn)

提供可能1影像技術(shù)和計算機技術(shù)的進步為精確放射治療的實現(xiàn)

提供可能10921103111屏氣技術(shù)舉例:ElektaABC4屏氣技術(shù)舉例:ElektaABC112四維CT影像技術(shù)呼氣吸氣螺旋開始時相由吸轉(zhuǎn)呼呼氣末由呼轉(zhuǎn)吸由吸轉(zhuǎn)呼呼氣吸氣螺旋開始呼吸曲線床位5四維CT影像技術(shù)呼氣吸氣螺旋開始時相由吸轉(zhuǎn)呼呼氣末由呼轉(zhuǎn)吸113影像引導放射治療技術(shù)

IGRT

40對葉片MLCKV級X射線球管KV級探測器陣列MV級探測器陣列6影像引導放射治療技術(shù)

IGRT40對葉片MLCKV級X射114在線校正—影像匹配7在線校正—影像匹配involvedlymphnodesOperableⅢa-N2Grade2:4.Grage4:1.paclitaxel200mg/m2757(P=0.Totalcases 38/281(13.RTisbetterthanOBS.RTisbetterthanOBS.ConcurrentChemo/RadioFavorGrHRbenefit%sur%

2y5y2y5ySEQCON-QDCON-BID二、早期非小細胞肺癌的放射治療UpdateofPORTLungCancer,2005.Pulmonarydisease: Positive:172,Negative:109G3急性和晚期非血液系統(tǒng)毒性：PV:順鉑/長春花堿SEQCON-QDCON-BIDPORT既能夠提高OS也能夠提高DSSNosurvivalbenefitoverconcurrenttherapyalone115一、放射治療在肺癌治療中的地位二、早期NSCL的放射治療三、局部晚期NSCL的放療/化療綜合治療四、3DCRT提高NSCLC的生存率五、術(shù)后放射治療involvedlymphnodes8一、放射治療在肺癌